Responses of Biomarkers of Folate and Riboflavin Status to Folate and Riboflavin Supplementation in Healthy and Colorectal Polyp Patients (The FAB2 Study)

Abstract

Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer. Riboflavin may interact with folate to modulate the effect. A double-blind randomized placebo-controlled intervention study (the FAB2 Study) was carried out in healthy controls and patients with colorectal polyps (adenomatous and hyperplastic) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk (DNA methylation and DNA damage; to be reported elsewhere). Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR C677T, and were randomized to receive 400 Mg of folic acid, 1,200 Mg of folic acid, or 400 Mg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks. Blood samples and colon biopsy samples were collected for the measurement of biomarkers of folate and riboflavin status. Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate, and a marked increase in RBC and plasma, with a dose-response. Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps. The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients. Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma, but with a suggestion of an upper limit. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2128 -35)

5,10‐Methylene‐tetrahydrofolate dissociates into tetrahydrofolate and formaldehyde at physiological pH and acidic pH, typical conditions used during sample extraction and LC‐MS/MS analysis of biological samples

“…Odin and coworkers discuss their results by referring to previous work (Liu et al, 2011;Kim et al, 1998;Powers et al, 2007;Elmore et al, 2007;Horne, 2001). Only two of the referred papers present data on 5,10-CH 2 -H 4 folate.…”

Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study

“…Some studies report a significant association between folate and vitamin B12 intake and status in older adults [2,15,16,17,18,19] while others do not [20,21,22]. Differences in folate and vitamin B12 bioavailability from total diets and specific food sources may provide a partial explanation for the observed discrepancies.…”

Relative Distribution of Folate Species Is Associated with Global DNA Methylation in Human Colorectal Mucosa

“…In fact, most human studies to date have used dietary folate assessment and/or blood folate concentration as surrogates for colorectal folate status (6,9,10). However, the relationship between blood and colonic mucosal folate concentration is unclear because of discrepancies in the results from previous studies (11)(12)(13)(14).…”